It has been known that there are certain gene abnormalities which occur with specificity and high frequency in cancer cells, and if a protein (proteins) which is caused by the gene abnormality is found, then such a protein may be a target molecule for cancer diagnosis and therapy. Among them, a group of molecules which belong to epidermal growth factor (EGF) family and their receptor ErbB family molecules have been the target molecules for cancer diagnosis and therapy as they are involved in the growth of cancer cells and related to malignancy. (J. Clin. Oncol., 17, 2639-2648 (1999); Biochem. Biophys. Acta., 1198, 165-184 (1994); Science, 244, 707-712 (1989); Anticancer Res., 20:91-95 (2000); Front. Biosci., 1;6:D685-707 (2001)).
It has been reported that epiregulin (EPR), a member of EGF family, has a bi-functional character that it promotes the growth of normal cells and inhibits the growth of certain cancer cells in vitro, and that the expression level of EPR (mRNA) in normal cells is extremely low except in the placenta and monocytes, but high in certain cancer cells (see, for example, The Journal of Biological Chemistry, 1995, Vol. 270, p. 7495-7500; The Biochemical Journal, 1997, Vol. 326, p. 69-75).
Further, in the clinical field, it is indicated that epiregulin may be a useful marker for cancer diagnosis because its expression is high in cancer of bladder cancer and the pancreatic cancer, (see, for example, Biochemical and Biophysical Research Communications, 2000, Vol. 14, 273 (3), p. 1019-1024; AntiCancer Research, 2000, January-February, 20 1A9: p. 91-95; Cancer Research, 2001, Vol. 61, p. 6227-6233).
Up until now, there have been reports that EPR polypeptide is detected using polyclonal antibodies (hEPR-PoAb) which recognize human epiregulin (hEPR) (see, for example, The Journal of Biological Chemistry, 1995, Vol. 270, p. 7495-7500; The Biochemical Journal, 1997, Vol. 326, p. 69-75), but they are not the methods with high sensitivity and high throughput because they require concentration operations, labeling with radioisotopes and the like, and there is no report of detecting EPR polypeptide in the living body. Thus, the establishment of a simple and highly sensitive method of detecting hEPR may offer useful means, as a cancer diagnosis method, for early detection of cancer.